Radiation therapies are commonly used to treat individuals with diseases such as cancer, and significant deleterious side effects can be associated with radiation therapies. These side effects can include, for example in the case of cranial radiation therapy, memory loss, neuron death, and cognitive decline. Other side effects can include damage to the visual system (Lessell, 2004), and damage to tissues of various internal organs and the vasculature. In many cases, the side effects associated with radiation therapy can be quite severe and even crippling. Thus, there exists a significant need for methods to ameliorate the deleterious side effects associated with radiation therapies.
Certain approaches have been evaluated in attempts to enhance the efficacy of radiation therapies. Phosphatidylinositol 3-kinase (PI3K) inhibitors, such as wortmannin and LY294002, have been shown to increase the sensitivity of tumor vasculature to destruction and apoptosis when given in combination with radiation therapies (Edwards et al., 2002; Tan and Hallahan, 2003; Geng et al., 2004). Inhibition of vascular endothelial growth factor receptor signaling using the sFLK-1 inhibitor SU5416 enhanced the destruction of tumor vasculature (Geng et al., 2001).
Inhibitors of glycogen synthase kinase 3 (GSK3) have been provided for use in treating ailments such as Alzheimer's and Parkinson's disease (Cohen and Goedert, 2004). Lithium is a GSK3 inhibitor that has been used as a mood-stabilizing drug for over fifty years, and lithium can protect neurons against several kinds of neurotoxic insults including trophic deprivation and excititoxicity (Hongsito et al., 2003; Nonaka et al., 1998; Klein and Melton 1996; Cimarosti et al., 2001; Hennion et al 2002; Nonaka and Chuang 1998; Jope, 2003). The potential for using a GSK3 inhibitor in combination with a radiation therapy has not been evaluated prior to the presently disclosed subject matter.